PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

A novel pH-sensitive magnetic alginate–chitosan beads for albendazole delivery

Background: Drug delivery system using polymer-coated magnetic carriers is considered as an effective strategy for passive targeting, which can not only increase drug utilization but also reduce the adverse reaction. With the carriers, sensitivity to physical stimuli (e.g., magnetic field, pH) has been developed and drugs were conjugated to form incorporating magnetic particles, so that drugs could be located to desire position. Method: Novel magnetic alginate (Alg)–chitosan (CS) beads loaded with albendazole (ABZ) were prepared and evaluated for pH sensitivity and drug release characteristics. The effects of six different factors (Alg concentration, the weight ratio of drug to polymer, the weight ratio of magnetite nanoparticles to polymer, CaCl2 concentration, CS concentration, the volume ratio of Alg to CS) were studied on the swelling ability of the magnetic beads. The magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, and vibrating sample magnetometry. In addition, the delivery behavior of ABZ from the magnetic beads was studied. Result: The magnetic Alg–CS beads had showed unique pH-dependent swelling behaviors and a continuous release of ABZ. From the magnetometer measurements data, the beads also had superparamagnetic property as well as fast magnetic response. Conclusion: The pH-sensitive magnetic beads may be used as a magnetic drug targeting system for ABZ in the gastrointestinal tract.     

Evaluation of pH-Sensitivity and Drug Release Characteristics of (Polyacrylamide-Grafted-Xanthan)–Carboxymethyl Cellulose-Based pH-Sensitive Interpenetrating Network Hydrogel Beads

Novel pH-sensitive interpenetrating network hydrogel beads of polyacrylamide-grafted-xanthan (PAAm-g-XG) and sodium carboxymethyl cellulose (NaCMC) loaded with ketoprofen were prepared and evaluated for pH sensitivity and drug release characteristics. The pH-sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting and alkaline hydrolysis reactions were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction studies were carried out to know the crystalline nature of encapsulated drug. Scanning electron microscopic study revealed that the interpenetrating polymer network (IPN) beads possess porous matrix structure in alkaline pH whereas nonporous matrix structure was observed in acidic pH. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline. The results of pulsatile swelling study indicated that the IPN beads changed their swelling behavior when pH of the external medium was altered. As pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all the beads. However, swelling process was slower than the deswelling. At higher pH values, the carboxyl functional groups of hydrogels undergo ionization and the osmotic pressure inside the beads increases resulting in higher swelling. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.     

Preparation and Evaluation Of Drug-Containing Chitosan Beads

Abstract

Sulfadiazine beads were prepared by dropping drug-containing solutions of the positively charged polysaccharide, chitosan, into tripolyphosphate (TPP) solutions. The droplets instantaneously formed gelled spheres by ionotropic gelation, entrapping the drug within a three-dimensional network of the ionically linked polymer. To achieve maximum drug content, high payloads, short gelation times, low TPP concentrations, and a low internal to external phase ratio were required. The chitosan beads showed pH-dependent swelling and dissolution behavior. The beads swelled and dissolved in 0.1N HCl, while they stayed intact in simulated intestinal fluid. The release of sulfadiazine in 0.1N HCl decreased with increasing concentration of TPP, but was independent of the TPP concentration in intestinal fluids. The morphology of the beads was investigated by scanning electron microscopy. The porosity of the beads depended on the method of drying.     

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads

Aim: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-β-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile.

Methods: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1?N HCl (pH 1.2) and phosphate buffer (pH 5.8).

Results: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730?±?0.05 to 0.890?±?0.03?mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12?h. The drug release from beads followed Fickian diffusion with swelling.

Conclusion: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.     

Dissolution Controlled Drug Release from Agarose Beads

Abstract

A simple method was used for loading ibuprofen or indomethacin into agarose beads to obtain sustained release. Placebo beads were prepared by a dropwise addition of a hot aqueous agarose solution into a beaker of chilled mineral oil and water. Prior to loading, the aqueous component in the beads was replaced by repeated soakings in ethanol. Loading was accomplished at room temperature using ethanolic drug solutions. Upon drying, the beads shrank to about a third of their original size. The surface morphology of dried placebo and loaded beads was studied using electron microscopy. The release time at 37° C and pH 7.5 increased with drug loading and at 50% loading the release time was 4 hours for indomethacin and 6 hours for ibuprofen. Release of chlorpheniramine from dried and swollen beads was examined to elucidate the release mechanism. From dissolution studies it was concluded that the delay due to swelling is less than 10 minutes, chlorpheniramine release from swollen beads was primarily diffusion controlled, and the release mechanism for indomethacin and ibuprofen has three components: i) swelling of the beads, ii) dissolution of crystallized drug, and iii) diffusion of dissolved drug from the beads.     

Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers

Abstract

Objective: The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug.

Methods: Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI.

Results: In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37?±?1.02% within 45?min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be “<28% and <60%”, respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads.

Conclusions: DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.     

Evaluation of hydrophilic matrix tablets based on Carbopol® 971P and low-viscosity sodium alginate for pH-independent controlled drug release

Background: The aim of this study was to evaluate matrix tablets containing different ratios of Carbopol^® 971P (CP) to low-viscosity sodium alginate (SA) and assess their suitability for pH-independent controlled drug release. Methods: Two processing methods (physical mixing, PM and spray-drying, SD) were applied before compaction and the release from corresponding matrices was compared. The release from CP-SA PM matrices was also investigated using three model drugs (paracetamol, salicylic acid, and verapamil HCl) and two dissolution media (0.1 N HCl or phosphate buffer, pH?=?6.8), and the release rate, mechanism, and pH-dependence were characterized by fitting of Higuchi and Peppas models, and evaluation of similarity factor. Furthermore, swelling behavior of CP-SA matrix tablets was studied for evaluating its impact on drug release. Results: The processing method (SD or PM) markedly affected the drug release from CP-SA matrices. ANOVA tests showed significant effects of the CP:SA ratio and drug type on the release rate (expressed by the constant, K_H, from Higuchi model) and of the dissolution medium on the release mechanism (expressed by the exponent, n, from Peppas model). Similarity factor (f₂) indicated that the CP:SA ratios ≥?25:75 and ≥?50:50 were suitable for pH-independent release of paracetamol and salicylic acid, respectively, although for verapamil HCl, the matrix with low CP:SA ratio (0:100) showed remarkably reduced pH-dependence of release. Swelling parameters (water uptake and mass loss) were significantly changed with experimental variables (CP:SA ratio, medium, and time) and were in good correlation with drug release. Conclusion: Matrix tablets based on CP and SA form a potentially useful versatile system for pH-independent controlled drug release.     

Evaluation of pH-sensitivity and drug release characteristics of (polyacrylamide-grafted-xanthan)-carboxymethyl cellulose-based pH-sensitive interpenetrating network hydrogel beads

Novel pH-sensitive interpenetrating network hydrogel beads of polyacrylamide-grafted-xanthan (PAAm-g-XG) and sodium carboxymethyl cellulose (NaCMC) loaded with ketoprofen were prepared and evaluated for pH sensitivity and drug release characteristics. The pH-sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting and alkaline hydrolysis reactions were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction studies were carried out to know the crystalline nature of encapsulated drug. Scanning electron microscopic study revealed that the interpenetrating polymer network (IPN) beads possess porous matrix structure in alkaline pH whereas nonporous matrix structure was observed in acidic pH. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline. The results of pulsatile swelling study indicated that the IPN beads changed their swelling behavior when pH of the external medium was altered. As pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all the beads. However, swelling process was slower than the deswelling. At higher pH values, the carboxyl functional groups of hydrogels undergo ionization and the osmotic pressure inside the beads increases resulting in higher swelling. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.     

Formulation,in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl

Context: Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs.

Objective: To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ).

Methods: Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12?h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied.

Results and discussion: The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3–4?min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO₂ gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer–Peppas model, which suggested that drug release was due to diffusion through polymer swelling.

Conclusion: Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.     

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12?h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.     

Design and in vitro characterization of buccoadhesive tablets of timolol maleate

Objective: The purpose of this work was to develop and evaluate buccoadhesive tablets of timolol maleate (TM) due to its potential to circumvent the first-pass metabolism and to improve its bioavailability.

Methods: The tablets were prepared by direct compression using two release modifying polymers, Carbopol 974P (Cp-974p) and sodium alginate (SA). A 3² full factorial design was employed to study the effect of independent variables, Cp-974p and SA, in various proportions in percent w/w, which influences the in vitro drug release and bioadhesive strengths. Physicochemical properties of the drug were evaluated by ultraviolet, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (P-XRD). Tablets were evaluated for hardness, thickness, weight variation, drug content, surface pH, swelling index, bioadhesive force and in vitro drug release.

Results: The FTIR and DSC studies showed no evidence of interactions between drug, polymers and excipients. The P-XRD study revealed that crystallinity of TM remain unchanged in optimized formulation tablet. Formulation F9 achieves an in vitro drug release of 98.967%?±?0.28 at 8?h and a bioadhesive force of 0.088 N?±?0.01211.

Conclusion: We successfully developed buccal tablet formulations of TM and describe a non-Fickian-type anomalous transport as the release mechanism.     

Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery

Objective: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.

Methods: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.

Results: Particles with an average size of 25–40?nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.

Conclusion: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.     

Propranolol Hydrochloride Binding in Calcium Alginate Beads

Abstract

The interaction of propranolol hydrochloride with alginate molecular chains in calcium alginate beads was investigated. The drug was either incorporated into formed calcium alginate gel beads or incorporated simultaneously with the gelation of alginate beads by Ca²⁺. Bed produced by the former method had a higher drug content and lower Ca²⁺ level compared to those prepared by the latter method. The extent of drug binding to the alginate molecules increased with decreasing Ca²⁺ levels in the beads, indicating that propranolol and Ca²⁺ shared common binding sites in the alginate chains, me appearance of the beads and the molphology of the alginate polymer in the beads were affected by the amounts of both propranolol and Ca²⁺ in the beads. Differential scanning calorimetry (DSC) analyses showed that the formation of the calcium alginate gel structure was impeded in the presence of propranolol molecules.     

Study of Formulation Variables on Properties of Drug-Gellan Beads by Factorial Design

ABSTRACT

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3³ factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85–1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48–98.28% w/w and 72.52–92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12–35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3–4 h in pH 7.4 phosphate buffer.     

Bead Coating Process Via an Excess of Crosslinking Agent

Abstract

Coated beads were prepared by soaking in sodium alginate solutions spherical matrices (beads) of carboxymethylcellulose crosslinked with aluminum chloride (AlCl3) and loaded with ambroxol hydrochloride as a model drug. The residual amount of the crosslinker induced an interfacial crosslinking reaction of the sodium alginate. Therefore, an insoluble, smooth and uniform in thickness coat was formed around the beads. As the coating time increased, the coat thickness increased until1 AlCl3 was present inside the beads. The rate of drug release from the coated beads was slower than that from the uncoated beads and decreased with the increase in coating time. Moreover, a constant rate phase, subsequent a burst period for the samples obtained with the highest coating times, was achieved. The dynamic swelling analysis allowed to exclude the influence of the polymer relaxation on the release process which appeared to be controlled by the alginate coat.     

Drug release behaviors of a pH/temperature sensitive core-shelled bead with alginate and poly(N-acryloyl glycinates)

In this study, a pH/temperature sensitive bead with core-shelled structure, as a drug carrier, was prepared by grafting of N-acryloylglycinates on the surface of sodium alginate beads. The pH and temperature sensitivity of the beads originate from sodium alginate (SA) and copoly(N-acryloylglycinates), respectively. Here, indomethacin (IMC) was selected as a drug model molecule and loaded in SA beads. The release of IMC was systematically investigated as a function of temperature, pH, and SA concentration. The amount of IMC released from beads was as high as 61.6%in pH = 7.4 phosphate buffer solution (PBS) over 620 min, whereas only 27.9% IMC diffused into the pH = 2.1 PBS. In addition, the release rates of IMC at 37.5°C were faster than that at 20.0°C and decreased with increasing SA concentration in the beads. The result indicates that the sensitive beads have the potential to be used as an effective pH/temperature-controlled delivery system in the biomedical fields.     

Controlled release multiple layer coatings

Purpose: In a fluid-bed coating machine, the coating solutions are normally sprayed using a manually controlled peristaltic pump. This study provides a process where two or more coating solutions can be sprayed consecutively using two or more syringe pumps controlled by a computer, to form multiple layers. In this process, the spraying parameters can be controlled easily from a computer. Methods: Propranolol HCl was used as a model drug. Nine different drug-loaded controlled release coated beads were prepared by using a combination of ethylcellulose and/or chitosan solutions. The pulse-coated beads were prepared by changing the spray rate and/or volume of the polymer solutions. Results: There was a fourfold increase (18 versus 75 minutes) in lag time when the same amount of ethylcellulose (4 g) was dissolved in 100 mL of ethanol instead of 160 mL. When the same amount of drug and ethylcellulose solution was applied on the acrylic coated beads as multiple layers coating, the lag time decreased to only 6 minutes. Similarly, the 50% drug release time also decreased significantly. Conclusion: An overall comparison of the dissolution profiles showed that drug release from these coated beads was changed significantly when the sequence of the drug and polymer layers was changed.     

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug

Objective: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug.

Methods: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG).

Results: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2?µm. The tablets prepared for WG disintegrated in time less than 30?min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC.

Conclusion: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.     

Effects of Microwave on Drug Release Property of Poly(Methyl Vinyl Ether-co-Maleic Acid) Matrix

ABSTRACT

The drug release behavior of beads made of poly(methyl vinyl ether-co-maleic acid) was investigated with respect to the influence of microwave irradiation. The beads were prepared by an extrusion method with sodium diclofenac as a model water-soluble drug. The beads were subjected to microwave irradiation at 80 W for 5 and 20 min, and at 300 W for 1 min 20 s and 5 min 20 s. The profiles of drug dissolution, drug content, drug-polymer interaction, and polymer-polymer interaction were determined by using dissolution testing, drug content assay, differential scanning calorimetry, and Fourier transform infra-red spectroscopy. Keeping the level of supplied irradiation energy identical, treatment of beads by microwave at varying intensities of irradiation did not bring about similar drug release profiles. The extent and rate of drug released from beads were markedly enhanced through treating the samples by microwave at 80 W as a result of loss of polymer-polymer interaction via the (CH₂)_n moiety, but decreased upon treating the beads by microwave at 300 W following polymer-polymer interaction via the O-H, COOH, and COO^? moieties as well as drug-polymer interaction via the N-H, O-H, COO^?, and C-O moieties. The beads treated by microwave at 300 W exhibited a higher level of drug release retardation capacity than those that were treated by microwave at 80 W in spite of polymer-polymer interaction via the (CH₂)_n moiety was similarly reduced in the matrix. The mechanism of drug release of both microwave-treated and untreated beads tended to follow zero order kinetics. The drug release was markedly governed by the state of polymer relaxation of the matrix and was in turn affected by the state of polymer-polymer and/or drug-polymer interaction in beads.